Double deckers are very efficient by design, but the newest airliners are nearly as efficient as (or even more efficient than) an A380.
1. It takes a long time to load that many people, so it only makes sense on long routes.
2. You need special facilities at the airport: bigger taxiways, special gates, large waiting areas, extra customs officials. This cuts into the profits.
3. Since there are so few routes, you won't have many 380s, but you still need a set of pilots trained on them, plus a reserve in case people get sick, can't make it to the airport, etc. That reserve crew isn't shared with your other smaller aircraft, so it's an additional expense. The same thing goes for maintenance.
4. Much of the theoretical fuel and maintenance economies of scale you get from flying a larger aircraft are lost with four engines instead of two.
EDIT: interesting link, that contradicts some of what I say above: https://leehamnews.com/2015/12/11/bjorns-corner-twins-or-qua...
Thus, twin engines have to have basically 100% reserve, while the 4 engines only need to have 33% reserve (to make up for one engine failing).